scholarly journals Knowledge about specific reversal agent of Greek AF patients on direct oral anticoagulants

2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
A Ioannidis ◽  
A Pechlevanis ◽  
A Pechlevanis ◽  
M Paraskelidou ◽  
M Paraskelidou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Antiplatelet Agents ◽  
City Hospital ◽  
Reversal Agent ◽  
Northern Greece ◽  
Waiting Room ◽  
Reversal Agents

Abstract Funding Acknowledgements Type of funding sources: None. Background Clinical guidelines recommend taking into account the patient’s preference when deciding on the options of direct oral anticoagulation (DOAC) therapy. Therefore, education is a prerequisite for informed, involved patients and patient-centred care. Purpose The aim of this study was to assess the patient’s awareness about the existence of the dabigatran specific reversal agent (Idarucizumab) and whether the patient was involved in the decision of the specific DOAC regimen. Methods Non-valvular atrial fibrillation (AF) patients on DOAC who visited the outpatient clinics of a city hospital in northern Greece were invited to participate. This project was part of the validation study of the Greek version of the Jessa Atrial fibrillation Knowledge Questionnaire. Analyses were performed by IBM SPSS Statistics. Results In total, there were 312 participants (168 females, 53.8%) with mean age: 64 ± 5.3 years old. The vast majority of patients (256, 82.1%) were not aware of the existence of any specific reversal agent regardless the socio-economic status (annual income, years of schooling) or the duration and type of AF. Patients that were switched from a vitamin-K antagonist (acenocoumarol) to a DOAC were more likely to be informed about specific reversal agents (31 out of 63 patients switched to DOAC, 49.2% vs. 10.0%, p < 0.05). Similarly, patients taking more than 5 pills per day were more likely to know about the reversal agent (41 of the 193 patients, 21.2% vs. 12.6%). Moreover, the majority of patients that reported any bleeding event that lead to seeking medical advice (minor or major bleeding) were informed about the specific reversal agent (35 out of 52 patients reporting bleeding event, 67.3% vs. 8.1%, p < 0.05). Inappropriately, only seven of the 38 patients (18.4%) that were also taking antiplatelet agents (mainly acetylsalicylic acid or clopidogrel) were aware of specific DOAC reversal agents. Patients with history of stoke or transient ischaemic attack were also better informed (38 out of 53 patients, 71.7% vs. 6.9%). Only about one of five patients on dabigatran (27 out of 129, 20.9%) knew about the dabigatran specific reversal agent, mainly from sources other than their doctor (e.g. journal in office waiting room). All patients agreed that they would prefer to have been informed about the current specific reversal agents when deciding on DOAC therapy. No data could be collected why patients who were informed about specific reversal agent were not prescribed dabigatran. Conclusions The sample of Greek non-valvular AF patients showed a noticeably low awareness of the existence of the specific DOAC reversal agent. It seems that DOAC prescription was a rather limited shared decision. Further research is warranted to confirm the aforementioned results.

scholarly journals Knowledge about atrial fibrillation and direct oral anticoagulation agents in Greek patients

2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
A Ioannidis ◽  
A Fragkiskou ◽  
M Paraskelidou ◽  
A Pechlevanis
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
City Hospital ◽  
Northern Greece ◽  
Funding Sources ◽  
Information Leaflets ◽  
Validated Questionnaire ◽  
Anticoagulation Agents

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) poses significant burden to patients, physicians, and healthcare systems globally. Patient knowledge about AF and its management is often limited though it is a perquisite for patient involvement and shared decision making. Direct oral anticoagulants (DOACs) are recommended for stroke prevention. Purpose The aim of this study was to assess the knowledge about AF and anticoagulation of AF patients. Methods Patients with AF on DOACs visiting the outpatient clinics of a city hospital in northern Greece were invited to participate. The Jessa AF Knowledge Questionnaire (JAKQ) was used (as part of the validation study of the Greek translation). Results In total, 285 patients participated (female 57.9%) with mean age 65 ± 13 years. The mean JAKQ score was 57.2 ± 17.4% corresponding to medium level of knowledge. Higher scores were positively associated with more schooling years and longer AF duration. The percentage of correct answer varied among the questions. One third of the participants answered wrongly (59 patients, 20.7%) or didn’t know (38 patients, 13.3%) what atrial fibrillation means. More than half of the patients didn’t know that AF is not always accompanied by symptoms and that medication cannot prevent AF permanently (154, 54.0% and 169, 59.3% respectively). The majority of patients knew that strokes are a consequence of AF and that blood thinners are prescribed in order to prevent clot formation (222, 77.9% and 226, 79.3% correspondingly). Moreover, most patients didn’t know correctly which painkiller they should prefer (177, 62.1%) and what to do when missing a dose (172, 60.4%). As expected patients who has experienced a bleeding event (minor or major that lead to medical care) scored higher (62.3% vs. 56.2%, p < 0.05). All patients replied that they would like to be offered more information (leaflets, online site, mobile applications, etc.). Conclusions A brief and validated questionnaire could be used to assess patients" knowledge of their condition and treatment, which would reveal important gaps. Further research is needed to evaluate if such an instrument could be used as a tool for individually tailored patient education.

scholarly journals Rates and Determinants for the Use of Anticoagulation Treatment before Stroke in Patients with Known Atrial Fibrillation

2020 ◽  
Vol 10 (2) ◽  
pp. 44-49
Author(s):  
Michela  Giustozzi ◽  
Giancarlo Agnelli ◽  
Silvia Quattrocchi ◽  
Monica Acciarresi ◽  
Andrea Alberti ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Medical Information ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antiplatelet Agents ◽  
Anticoagulant Treatment ◽  
Anticoagulation Treatment

Introduction and Objective: Even though the introduction of less cumbersome anticoagulant agents has improved, the rates ofoverall anticoagulant treatment in eligible patients with atrial fibrillation (AF) remain to be defined. We aimed to assess the rates of and determinants for the use of anticoagulation treatment before stroke in patients with known AF since the introduction of direct oral anticoagulants (DOAC) in clinical practice. Methods: Consecutive patients admitted to an individual stroke unit, from September 2013 through July 2019, for acute ischemic stroke or transient ischemic attack (TIA) with known AF before the event were included in the study. Logistic regression analysis was used to identify independent predictors of the use of anticoagulant treatment. Results: Overall, 155 patients with ischemic stroke/TIA and known AF were included in this study. Among 152 patients with a CHA2DS2-VASc score >1, 43 patients were not receiving any treatment, 47 patients were receiving antiplatelet agents, and the remaining 62 patients were on oral anticoagulants. Among 34 patients on DOAC, 13 were receiving a nonlabeled reduced dose and 18 out of 34 patients on vitamin K antagonists had an INR value <2 at the time of admission. Before stroke, only 34 out of 155 patients (21.9%) were adequately treated according to current guidelines. Previous stroke/TIA was the only independent predictor of the use of anticoagulant therapy. Conclusions: Only 21.9% of the patients hospitalized for a stroke or TIA with known AF before the event were adequately treated according to recent treatment guidelines. It is important to improve medical information about the risk of AF and the efficacy of anticoagulants in stroke prevention.

Anticoagulation Changes Following Major and Clinically Relevant Nonmajor Bleeding Events in Non-valvular Atrial Fibrillation Patients

2021 ◽  
pp. 089719002110641
Author(s):  
Thane Feldeisen ◽  
Constantina Alexandris-Souphis ◽  
Brian Haymart ◽  
Xiaowen Kong ◽  
Eva Kline-Rogers ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Drug Class ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Event ◽  
Bleeding Events ◽  
Anticoagulation Management ◽  
Anticoagulation Clinics ◽  
The Individual

Background Bleeding events are common complications of oral anticoagulant drugs, including both warfarin and the direct oral anticoagulants (DOACs). Some patients have their anticoagulant changed or discontinued after experiencing a bleeding event, while others continue the same treatment. Differences in anticoagulation management between warfarin- and DOAC-treated patients following a bleeding event are unknown. Methods Patients with non-valvular atrial fibrillation from six anticoagulation clinics taking warfarin or DOAC therapy who experienced an International Society of Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant non-major (CRNM) bleeding event were identified between 2016 and 2020. The primary outcome was management of the anticoagulant following bleeding (discontinuation, change in drug class, and restarting of same drug class). DOAC- and warfarin-treated patients were propensity matched based on the individual elements of the CHA2DS2-VASc and HAS-BLED scores as well as the severity of the bleeding event. Results Of the 509 patients on warfarin therapy and 246 on DOAC therapy who experienced a major or CRNM bleeding event, the majority of patients continued anticoagulation therapy. The majority of warfarin (231, 62.6%) and DOAC patients (201, 81.7%) restarted their previous anticoagulation. Conclusion Following a bleeding event, most patients restarted anticoagulation therapy, most often with the same type of anticoagulant that they previously had been taking.

Managing reversal of direct oral anticoagulants in emergency situations

2016 ◽  
Vol 116 (12) ◽  
pp. 1003-1010 ◽  
Author(s):  
Harry R. Büller ◽  
Anna Falanga ◽  
Werner Hacke ◽  
Jeroen Hendriks ◽  
Trudie Lobban ◽  
...  
Keyword(s):  
Task Force ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Therapeutic Benefit ◽  
Current Status ◽  
Reversal Agent ◽  
Medical Specialties ◽  
Reversal Agents ◽  
Emergency Situations

SummaryAnticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24–7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

Cost Analysis of Direct Oral Anticoagulants Compared with Warfarin in Patients with Blunt Traumatic Intracranial Hemorrhages

2018 ◽  
Vol 84 (6) ◽  
pp. 1010-1014 ◽  
Author(s):  
Laura C. Lamb ◽  
Monica Difiori ◽  
Christopher Comey ◽  
James Feeney
Keyword(s):  
Hospital Admission ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cost Benefit ◽  
Antiplatelet Agents ◽  
Trauma Patients ◽  
Reimbursement Rate ◽  
Reversal Agents ◽  
Level Ii ◽  
Traumatic Intracranial Hemorrhage

Direct oral anticoagulants (DOACs) are rapidly gaining popularity as alternatives to warfarin in the prevention of stroke or systemic embolic events because of the simplicity of their dosing and lack of monitoring requirement. Many physicians feared that these novel agents would be cost-prohibitive not only in their administration but also in their sequelae of bleeding, given the few reversal agents available. Whereas the medication itself is more expensive than traditional warfarin, the total cost of a hospital admission has not been compared between patients on DOACs and warfarin who have sustained a blunt traumatic intracranial hemorrhage (ICH). We conducted a retrospective review of our hospital's trauma database from June 2011 through September 2015 at our Level II trauma center of patients who suffered from an ICH who were anticoagulated at the time of their trauma. Patients who died during their hospital admission or were exclusively on antiplatelet agents were excluded. Of the 136 patients studied, 79 were on warfarin and 57 were on a DOAC at the time of their presentation for a traumatic ICH. The average charged cost for the hospital stay of a patient with an ICH was significantly higher for patients on warfarin compared with DOACs [$70,384.08 vs $49,226.66 (P = 0.02)]. The average reimbursement rate for the hospital was also significantly higher for those patients on warfarin as compared with those on DOACs [$23,922.93 vs $14,705.77 (P = 0.02)]. DOACs are associated with a significant cost benefit in patients admitted for blunt traumatic ICHs when compared with those on warfarin.

scholarly journals Algorithm for the Choice of Anticoagulant for Patients with Atrial Fibrillation

2020 ◽  
Vol 16 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Yu. P. Skirdenko ◽  
N. A. Nikolaev
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Food Preferences ◽  
Antiplatelet Agents ◽  
Thromboembolic Complications ◽  
Adherence To Treatment ◽  
Treatment Optimization ◽  
Initial Examination ◽  
Hemorrhagic Complications

Aim. To evaluate the effectiveness of the anticoagulant choice algorithm in the prevention of complications of atrial fibrillation (AF). Material and methods. Patients with AF (n=98) were included into observational prospective study. The level of adherence to treatment, risk of food interactions and presence of CYP2C9 and VKORC1 genes mutations were determined at the initial examination. These indicators were necessary to specify an eligible anticoagulant according to the evaluated algorithm. Therapy was prescribed by the attending physician. Hemorrhagic and thromboembolic complications were assessed at the next examination after 24 weeks. Results. Hemorrhagic complications were observed in 31.6% of patients during the follow-up. Their number was comparable in individuals taking antiplatelet agents and direct oral anticoagulants (DOACs) (χ2=1.44; p<0.49, Pearson) and significantly more in individuals taking warfarin (as compared to DOACs: χ2=25.08; p<0.000, Pearson; and antiplatelet agents: χ2=34.32; p<0.000, Pearson). Thromboembolic complications were reported in 8.16% of patients. Their number was more in patients taking DOACs than warfarin (χ2=7.03; p<0.03, Pearson). Patients who had to take DOACs according to the algorithm, but in the study took warfarin, demonstrated significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Patients who could take warfarin according to the algorithm, but in the study took DOACs, had significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Conclusion. The results of the study demonstrated the potential for reduction in complications, especially thromboembolic, in the choice of anticoagulant using the algorithm; and reduction in complications of therapy, primarily with warfarin, due to the initial prescription of DOACs. The proposed approach, which consists in using the quantitative assessment of adherence to treatment, and only if necessary supplemented by the assessment of food preferences and/or pharmacogenetic studies, contributes to the treatment optimization.

scholarly journals Direct Oral Anticoagulants after Ischemic Stroke: Which Patient? Which Drug? And How Early?

2021 ◽  
Vol 41 (01) ◽  
pp. 031-034
Author(s):  
Gian Marco De Marchis
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

AbstractDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and ischemic stroke. The main advantage of DOAC over VKA is the lower rate of bleeding and mortality. This review covers challenges clinicians can encounter when treating patients with AF and ischemic stroke, including timing of DOAC start and ongoing randomized clinical trials, appropriate dosing, and available comparative evidence across DOACs. For patients without AF but with an ischemic stroke, the review outlines the role of DOACs. Finally, the risk of thrombotic events associated with specific DOAC reversal agents and DOAC pausing is reviewed.

scholarly journals Outcomes of Direct Oral Anticoagulants with Aspirin Versus Warfarin with Aspirin for Atrial Fibrillation and/or Venous Thromboembolic Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 179-179
Author(s):  
Jordan K Schaefer ◽  
Josh Errickson ◽  
Xiaowen Kong ◽  
Tina Alexandris-Souphis ◽  
Mona A Ali ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Thromboembolic Disease ◽  
Venous Thromboembolic Disease ◽  
Advisory Committees ◽  
Venous Thromboembolic ◽  
History Of

Abstract Introduction The direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are increasingly utilized for the management of venous thromboembolic disease (VTE) and/or non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to warfarin or DOAC therapy increases bleeding risk. Patients on combination therapy with ASA and an anticoagulant were not well represented in clinical trials comparing DOACs to warfarin. We sought to compare bleeding and thrombotic outcomes with DOACs and ASA compared to warfarin and ASA in a non-trial setting. Methods We conducted a retrospective registry-based cohort study of adults on DOAC or warfarin therapy for VTE and/or NVAF. Warfarin treated patients were followed by six anticoagulation clinics. Four out of the six clinics contributed data on their patients that were on DOACs in the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) from January 2009 to June 2021. Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (warfarin+ASA vs DOAC+ASA) of patients were analyzed based on ASA use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results We identified a total of 1,139 patients on DOACs plus ASA and 4,422 patients on warfarin plus ASA. After propensity matching, we compared two groups of 1,114 matched patients. DOAC treated patients were predominately on apixaban (62.3%) and rivaroxaban (30.4%), most often at therapeutic doses (Table 1). Patients were largely (90.5%) on low dose ASA (≤ 100 mg). Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for a median of 11.7 months (interquartile range 4.4 and 34 months). Patients treated with DOAC+ASA had 2.4 thrombotic events per 100 patient years compared to 2.2 thrombotic events per 100 patient years with warfarin+ASA (P=0.78). There were no significant differences observed between groups by thrombotic subtype (stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, table 1). Bleeding was also similar with 30.1 bleeding events per 100 patient years with DOAC+ASA compared to 27.8 bleeds per 100 patient years with warfarin+ASA (P=0.24). There were no significant differences by bleeding subtype (table 1). Hospitalizations for clotting occurred less frequently with DOAC+ASA (0.9 hospitalizations per 100 patient years) compared to warfarin+ASA (1.7 hospitalizations per 100 patient years, P=0.03). Mortality, transfusions, and healthcare utilization were otherwise similar between the two groups. Conclusions For patients on a DOAC versus warfarin with ASA for atrial fibrillation and/or venous thromboembolic disease without a recent myocardial infarction or heart valve replacement, bleeding and thrombotic outcomes were similar. Figure 1 Figure 1. Disclosures Kaatz: Gilead: Consultancy; CSL Behring: Consultancy; Novartis: Consultancy; Bristol Myer Squibb: Consultancy, Research Funding; Pfizer: Consultancy; Alexion: Consultancy; Janssen: Consultancy, Research Funding; Osmosis Research: Research Funding. Kline-Rogers: Janssen: Consultancy; American College of Physicians: Consultancy. Sood: Bayer: Consultancy. Froehlich: Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Boehringer-Ingelheim: Consultancy; Pfizer: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; Fibromuscular Disease Society of America: Research Funding. Barnes: National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Acelis: Consultancy; AMAG Pharmaceuticals: Consultancy; Connected Health: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; AC Forum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy.

Abstract 15163: Differences in Preferences Between Physicians and Patients for the Use and Dosing of Direct Oral Anticoagulants for Atrial Fibrillation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jennifer A Rymer ◽  
Debbe McCall ◽  
Mellanie T Hills ◽  
Tracy Y Wang
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Primary Care Providers ◽  
Severe Bleeding ◽  
Minor Bleeding ◽  
Care Providers ◽  
Reversal Agent ◽  
Physician Knowledge ◽  
Reduced Dose

Introduction: Direct oral anticoagulants (DOACs) are effective in reducing the risk of stroke for patients with atrial fibrillation (AF) only if prescribed at the labeled dose. Little is known about patient or clinician preferences for DOAC selection and dosing. Methods: We consented 240 physicians treating ≥20 patients with AF and 343 patients with AF. Physician knowledge of DOAC dosing was tested with 4 hypothetical patient case scenarios. Both patients and physicians were asked to grade the importance of 25 factors in anticoagulation decision-making. Results: Among physicians, the median age was 55 years, 13% were female, 23% were primary care providers. Most physicians (63%) stated empirically they would never/rarely use an adjusted lower dose if the patient did not meet dose adjustment criteria. However, in hypothetical case scenarios of a patient indicated for full dose DOAC, 40.8% of clinicians under-dosed apixaban (<5 mg bid daily) and 17.1% for rivaroxaban (<20 mg daily). In scenarios where a patient met dosing criteria for reduced dose DOAC, 64.6% (apixaban 2.5 mg bid daily) and 71.7% (rivaroxaban 15 mg daily) of physicians chose the reduced dose DOAC answer. Only 32.1% of clinicians answered all 4 scenarios correctly. Among patients with AF, the median age was 65 years, 74% were female, 85% had AF >1 year and 89% were currently anticoagulated. Patients and physicians both ranked stroke prevention and avoiding severe bleeding very important when choosing a DOAC. Physicians were more likely than patients to rank cost as very important, patients were more likely than physicians to consider the following very important: may cause minor bleeding, the dose of med can be reduced if need to, reversal agent available, and how long the drug has been on market ( Figure ). Conclusions: DOAC dosing strategies may be driven by gaps in physician knowledge, on top of varying treatment beliefs and preferences between physicians and patients.

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